Antibacterial and antithrombotic medical catheter and preparation method thereof

Abstract

The invention discloses an antibacterial and antithrombotic medical catheter and a preparation method thereof. According to the medical catheter, a hydrogel coating is prepared on the surface of the medical catheter, the hydrogel coating contains a three-layer structure, and the medical catheter has low swelling property and excellent mechanical property, stability, durability, platelet adhesion resistance, antibacterial property and biocompatibility. The preparation method disclosed by the invention is simple, efficient and environment-friendly; the dopamine layer provides strong adhesion performance, glucose oxidase entrapped in FDA provides longer-term antibacterial performance, and finally the carboxylic acid betaine zwitterionic coating is introduced to further enhance the antithrombotic performance of the hydrogel coating, so that the hydrogel coating medical catheter is produced. The invention provides a new strategy for the low-expansion amphiphilic ion hydrogel coating with antithrombotic and antibacterial properties in the field of biomedical materials, especially as a medical catheter, and the coating can be applied to biomedical equipment in contact with blood.

Description

Technical Field

[0001] The present invention belongs to the technical field of polymer hydrogels, and particularly relates to a medical catheter for antibacterial and antithrombotic and a preparation method thereof. Background Art

[0002] Biomedical materials have become effective tools for combating diseases due to their excellent biocompatibility, bio - substitutability, and blood compatibility. Currently, biomedical devices such as catheters, interventional tubes, vascular stents, and mechanical heart valves are widely used in clinical practice. However, challenges such as thrombosis, bacterial infection, and inflammation remain inevitable complications in the clinical use of biomedical devices. Research shows that bacteria initially adhere to the material surface in a non - specific manner, continuously secrete extracellular matrix, form bacterial biofilms on the surface, and then proliferate. In addition, binding sites on the thrombus - forming surface can promote bacterial adhesion and biofilm formation, leading to the development of infection. When infection occurs, bacteria stimulate the production of pro - inflammatory cytokines, triggering a severe inflammatory response. Traditionally, a common method in clinical practice is to coat biomedical devices with antibiotics to relieve bacterial infection and inflammation. However, over - use of antibiotics may lead to drug resistance, and the validity period of antibiotics is limited, unable to completely solve the problems of bacterial infection and inflammation. Therefore, compared with antibiotics, preventing or resisting the occurrence of biomaterial - related infections by initially inhibiting bacterial adhesion is safer and more effective.

[0003] Yao et al. prepared a poly(carboxybetaine) microgel - reinforced poly(sulfobetaine) (pCBM / pSB) pure zwitterionic hydrogel with excellent mechanical stability and anti - swelling properties. The pCBM / pSB hydrogel coating was adhered to the PVC substrate through an entanglement network between pSB and PVC chains. This catheter can not only reduce the foreign body reaction but also prevent in vitro thrombus formation in the blood circulation of rats and rabbits without anticoagulants. It was confirmed that it is suitable as a medical catheter for clinical applications (Yao, M., Wei, Z., Li, J. et al. Microgel reinforced zwitterionic hydrogel coating for blood - contacting biomedical devices. Nat Commun 13, 5339(2022).)

[0004] Zwitterionic hydrogels are well-known for their antifouling properties achieved by strongly binding water molecules to the zwitterionic moieties of their side chains and have been widely used in the field of biomedical materials. They can tightly bind a large amount of water molecules through electrostatic interactions to form a barrier to resist non-specific protein adhesion. Considering that the antibacterial application of polymer coatings in medical devices that require long-term intervention or implantation still has limitations. Their poor mechanical properties and low substrate adhesion hinder their application as coating materials for biomedical devices. Therefore, it is necessary to design a medical catheter that can sterilize, antibacterial, and resist thrombosis for a longer time. The hydrogel coating on the catheter contains a three-layer structure, with low swelling, excellent mechanical properties, stability, durability, antiplatelet adhesion, antibacterial properties, and biocompatibility. Summary of the Invention

[0005] The purpose of the present invention is to overcome the disadvantages of complex preparation processes, poor mechanical properties, and low substrate adhesion in the prior art, and to provide a medical catheter based on zwitterions for antibacterial and antithrombotic purposes and its preparation method, achieving the following purposes: First, explore a certain process to make its preparation process more simple and efficient, and find the best formula for the hydrogel coating; Second, explore the best preparation plan for the hydrogel coating to make it stable and have optimal performance; Third, the hydrogel dressing has suitable mechanical properties, anti-swelling ability, antiplatelet adhesion ability, and excellent antibacterial adhesion ability effect; Fourth, simplify the preparation.

[0006] To achieve the above objectives, the present invention adopts the following technical solutions:

[0007] A preparation method of a medical catheter for antibacterial and antithrombotic purposes, comprising the following steps:

[0008] 1) Acrylate poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymer to synthesize Pluronic diacrylate FDA;

[0009] 2) Mix FDA with glucose oxidase to form FDA self-assembled micelles, and glucose oxidase is encapsulated in the micelles;

[0010] 3) Immerse the silicone catheter in the adhesive to deposit a bonding layer on the surface of the silicone catheter;

[0011] 4) Mix a sulfobetaine-type zwitterionic monomer, a cross-linking agent, FDA self-assembled micelles encapsulated with glucose oxidase, an oxidant, an initiator, and water to prepare a prepolymer solution;

[0012] 5) Immerse the silicone catheter with the bonding layer prepared in step 2) in the prepolymer solution to bond an antibacterial and antithrombotic hydrogel coating on the surface of the silicone catheter, rinse, and dry;

[0013] 6) Immerse the silicone catheter processed in step 4) in the initiator solution;

[0014] 7) Immerse the silicone catheter processed in step 5) in the carboxybetaine zwitterionic monomer solution, deoxygenate, and irradiate with ultraviolet light to cover the carboxybetaine zwitterion on the hydrogel coating. Take it out and dry to obtain a medical catheter based on zwitterions for antibacterial and antithrombotic functions.

[0015] Further, the acrylation degree of the FDA self-assembled micelles in step 2) is 10-15%.

[0016] Further, the adhesive in step 3) is a dopamine hydrochloride solution, and the concentration of dopamine hydrochloride is 1.0-5.0 mg / mL; the dopamine hydrochloride deposition process lasts for 24 h, and the dopamine hydrochloride solution is replaced every 3 h.

[0017] Further, the initiator is α-ketoglutaric acid; the oxidant is ferric chloride; the cross-linking agent is methylene bisacrylamide; the sulfobetaine-type zwitterionic monomer is sulfobetaine methacrylate, and the carboxybetaine zwitterionic monomer is carboxybetaine methacrylate.

[0018] Further, in the prepolymer solution, the concentration of the sulfobetaine-type zwitterionic monomer is 3.0-6.0 mol / L; the concentration of the pluronic diacrylate self-assembled micelles is 50-400 mg / mL; the concentration of the cross-linking agent is 1-5 mg / mL; the concentration of ferric chloride is 1-5 mg / mL.

[0019] Further, the immersion time of the silicone catheter in the prepolymer solution in step 5) is 30 min.

[0020] Further, the immersion time of the initiator solution in step 6) is 2-10 min.

[0021] Further, in step 7), deoxygenation is carried out by introducing nitrogen or inert gas to reduce the oxygen solubility; the concentration of the carboxybetaine zwitterion is 3.0-6.0 mol / L; the ultraviolet light wavelength is 350-380 nm, and the irradiation time is 6-12 h.

[0022] A medical catheter for antibacterial and antithrombotic functions prepared by the above preparation method.

[0023] In summary, the present invention has the following beneficial effects: The preparation method is simple, efficient and environmentally friendly, and is friendly to the environment; the hydrogel coating on the medical catheter consists of a three-layer structure; the adhesive side of the hydrogel coating forms a firm adhesion through the excellent adhesion performance of the adhesive dopamine, and then in-situ grows a sulfobetaine zwitterionic hydrogel coating; finally, a carboxybetaine hydrogel coating is prepared by interpenetrating network; the present invention has appropriate mechanical properties, anti-nonspecific protein adhesion ability, anti-cell adhesion ability, biocompatibility and excellent antibacterial effect. The addition of FDA improves the anti-swelling property and mechanical properties of the hydrogel coating. GOx is encapsulated in the FDA micelles and can utilize the H 2 O 2 produced by GOx decomposing glucose during bacterial adhesion for sterilization. Since GOx is encapsulated in the micelles, the release of GOx is restricted, thus achieving a slow release effect. Compared with the existing effect of directly encapsulating GOx in the hydrogel, it has the ability of long-term sterilization and anti-thrombosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Scanning electron microscope images at each stage after the hydrogel coating prepared in Example 12 is completed.

[0025] Figure 2 Scanning electron microscope picture of anti-platelet adhesion after the catheter in Example 15.

[0026] Figure 3 Fluorescence microscope images of bacterial adhesion of the bare silicone catheter and the medical catheter with hydrogel coating in Example 13 after co-culturing in Escherichia coli (E. coli) bacterial solution for 24 hours and 120 hours.

[0027] Figure 4 Schematic diagram after the catheter with hydrogel coating in Example 16 is applied in mice.

[0028] Figure 5 Schematic diagram after the catheter with hydrogel coating in Example 16 is taken out from mice and the bacteria are cultured. DETAILED DESCRIPTION OF THE INVENTION

[0029] The following gives a detailed introduction to the implementation mode of the present invention in combination with the specification drawings and examples, but the protection scope of the present invention is not limited thereto.

[0030] Unless otherwise specified, the raw materials used in the embodiments of the present invention are all commercially available or raw materials that can be obtained by those skilled in the art; unless otherwise specified, the methods used in the embodiments of the present invention are all methods mastered by those skilled in the art.

[0031] Examples 1-9

[0032] Preparation of an antibacterial and antithrombotic hydrogel layer, including the following preparation steps:

[0033] 1) Acrylate poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymer to synthesize Pluronic diacrylate (FDA), with an acrylation degree of 10.4%;

[0034] 2) Mix FDA with glucose oxidase to form FDA self-assembled micelles, and glucose oxidase is encapsulated in the micelles;

[0035] 3) Mix sulfobetaine zwitterionic monomer, methylene bisacrylamide, FDA self-assembled micelles encapsulated with glucose oxidase, oxidant ferric chloride, initiator α-ketoglutaric acid and water to prepare a prepolymer solution. The sulfobetaine zwitterionic monomer is methyl methacrylate sulfobetaine with a concentration of 4 mol / L, the concentration of the crosslinking agent methylene bisacrylamide is 2 mg / mL; the concentration of ferric chloride is 2 mg / mL, and the dosage of the initiator α-ketoglutaric acid is 2.0 mol% relative to the sulfobetaine zwitterionic monomer. The addition amounts of FDA, glucose oxidase and water are shown in Table 1;

[0036] 4) Add the prepolymer solution prepared in step 3) into a mold, and after thermal initiation polymerization at 60 °C for 30 min, form a cylindrical hydrogel (diameter: 10 mm, height: 5 mm) to obtain pSBMA / FDA@GOx hydrogel.

[0037] Table 1 Summary of the dosage of some raw materials in Examples 1-10

[0038]

[0039]

[0040] Example 10

[0041] The anti-swelling property of the hydrogel was evaluated by the equilibrium swelling experiment: The cylindrical hydrogels prepared in Examples 1-9 were tested for anti-swelling property. They were dried at 60 °C for 6 hours, and the hydrogels were weighed and recorded as W 0 , then, the hydrogels were immersed in PBS buffer solutions at different temperatures (37 °C and 20 °C). The swollen hydrogels were taken out regularly, and the excess water on the surface of the hydrogels was removed with filter paper. The weight of the swollen hydrogels was recorded until the weight no longer increased, and the final weight was recorded as Wt. The swelling ratio of the hydrogel was calculated using the following formula, and the results are shown in Table 2:

[0042]

[0043] Table 2 Swelling ratios of hydrogel coatings with different FDA contents at different temperatures

[0044] FDA concentration (mg / mL) 0 50 100 150 200 250 300 350 400 Swelling rate % (20 °C) 396.65 379.69 315.49 283.33 240.67 168.77 286.3 327.85 382.3 Swelling rate % (37 °C) 380.34 303.752 252.392 226.66 192.536 125.016 220.23 234.18 254.87

[0045] FDA is a PEO-PPO-PEO triblock copolymer. At room temperature, the hydrophilic PEO shell and PPO core of FDA self-assemble into micelles; at 37 °C, the hydrophobic interaction between PPO chains is enhanced, resulting in the contraction of the PPO core, which offsets the extension of the hydrophilic PEO chains, and the hydrogel hardly swells. As the amount of FDA added increases, the swelling ratio becomes lower and lower. When the addition amount of FDA reaches 250 mg / ml, it is only 125%. When the amount of FDA reaches 300 mg / ml and 400 mg / ml, there will be poor mutual solubility between FDA and SBMA, and when the swelling equilibrium is reached, the hydrogel will split. Therefore, considering comprehensively, the optimal addition amount of FDA is 250 mg / ml.

[0046] Example 11

[0047] Testing the compressive stress of the hydrogel: At room temperature, the mechanical properties of the pSBMA / FDA@GOx hydrogels prepared according to Examples 1, 3-6 were tested using a universal testing machine (Instron 5966, USA) at the ambient air temperature. The compression range was 0-80%, and the fixed compression rate was 5 mm / min. The test results are shown in Table 3. The compressive stress increases with the increase in the amount of FDA added. The maximum compressive stress can reach 134.27 kPa when the amount of FDA added is 250 mg / mL.

[0048] Table 3 Compressive stress of hydrogels with different FDA contents prepared in Examples 1, 3 to 6

[0049] FDA concentration (mg / mL) 0 100 150 200 250 Compressive stress (MPa) 12 22.74 26.28 47.52 134.27

[0050] Example 12

[0051] 1) Acrylate poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymer to synthesize Pluronic diacrylate FDA, with an acrylation degree of 10.4%;

[0052] 2) Mix FDA with glucose oxidase to form FDA self-assembled micelles, and glucose oxidase is encapsulated in the micelles;

[0053] 3) Immerse the silicone catheter in a dopamine hydrochloride solution with a concentration of 2.0 mg / mL. When depositing dopamine hydrochloride, change the solution every 24 hours and replace the dopamine hydrochloride solution every 3 h to deposit a layer of polydopamine on the surface of the silicone catheter;

[0054] 4) Mix the sulfobetaine-type zwitterionic monomer, methylene bisacrylamide, FDA self-assembled micelles encapsulating glucose oxidase, the oxidant ferric chloride, the initiator α-ketoglutaric acid, and water to prepare a prepolymer solution. The sulfobetaine-type zwitterionic monomer is sulfobetaine methacrylate methyl ester with a concentration of 4 mol / L, the concentration of the crosslinking agent methylene bisacrylamide is 2 mg / mL; the concentration of ferric chloride is 2 mg / mL, and the dosage of the initiator α-ketoglutaric acid is 2.0 mol% relative to the sulfobetaine-type zwitterionic monomer. The addition amounts of FDA, glucose oxidase, and water are the same as in Example 6;

[0055] 5) Immerse the silicone catheter in the prepolymer solution and react for 30 min; then rinse the surface with deionized water and dry it in an oven at 60 °C for 6 hours;

[0056] 6) Immerse the silicone catheter in the α-ketoglutaric acid solution for 2 min;

[0057] 7) Then place the silicone catheter into 4.0 mol / L carboxybetaine methacrylate methyl ester, and deoxygenate it by introducing nitrogen to reduce the oxygen solubility. Irradiate it with a UV lamp with a wavelength of 380 nm for 8 h. After the reaction, dry it in the air. After completion, a uniform zwitterion-based medical catheter with antibacterial and antithrombotic properties for vision is obtained, denoted as pCB / pSBMA / FDA@GOx.

[0058] For the bare silicone catheter at each stage of the preparation process ( Figure 1 A therein), the silicone catheter coated with polydopamine ( Figure 1 B therein), the pSBMA / FDA@GOx silicone catheter coated with a hydrogel layer ( Figure 1 C therein), and the silicone catheter coated with a pCB / pSBMA / FDA@GOx layer ( Figure 1 D therein), perform electron microscope image scanning. The dopamine layer, the sulfobetaine-type zwitterionic layer, and the carboxybetaine zwitterionic layer are all successfully prepared, and the coating thickness has corresponding changes.

[0059] Measure the water contact angle of the coating at each stage after preparation. The water contact angles of the prepared hydrogel coatings are shown in Table 4. It can be seen from Table 4 that the dopamine layer, the sulfobetaine-type zwitterionic layer, and the carboxybetaine zwitterionic layer are all successfully prepared, and the water contact angles have corresponding changes.

[0060] Table 4 Water contact angles of the hydrogel coatings of each layer prepared in Example 12

[0061]

[0062] Example 13

[0063] Antibacterial adhesion test: According to the steps of Example 6, a pSBMA / FDA hydrogel was prepared without adding glucose oxidase. A bare silicone catheter, pSBMA / FDA hydrogel (not encapsulated with glucose oxidase, lacking the encapsulation process of glucose oxidase, and other steps were the same as in Example 6), the pSBMA / FDA@GOx hydrogel prepared in Example 6, and the pCB / pSBMA / FDA@GOx hydrogel-coated catheter prepared in Example 12 were placed in an Escherichia coli (E. coli) solution with an optical density (OD) of 0.1. The microplate was placed in a constant temperature shaker at 37 °C and cultured at 120 rpm for an appropriate time. After the co-culture ended, all samples were rinsed 3 times with sterile PBS and stained with the Live / Dead BacLight viability kit for 10 min in the dark, then rinsed 3 times with sterile PBS, and the bacterial adhesion on the surface of the samples was observed under an inverted fluorescence microscope. The antibacterial experiments at 24 hours and 120 hours were as Figure 3 shown. The hydrogel coatings showed excellent anti-adhesion to E. coli, and almost no live bacteria adhered to their surfaces. At the same time, a small amount of dead bacteria could be observed, which was due to the bactericidal effect of glucose oxidase. Moreover, during the 120-hour antibacterial experiment, the hydrogel coatings still had excellent anti-adhesion performance, which was due to the slow release and long-lasting antibacterial effect of GOx caused by the FDA immobilization method, indicating that the hydrogel coatings had excellent antibacterial effects.

[0064] Example 14

[0065] Anti-protein adhesion test: A bare silicone catheter, a silicone coated with pSBMA / FDA@GOx hydrogel (Example 6), and a silicone sample (5 mm × 5 mm × 3 mm) coated with pCB / pSBMA / FDA@GOx hydrogel of Example 12 were placed in a 24-well plate, and 1 mL of HRP-IgG was added to each plate. After the samples were placed in a constant temperature incubator at 37 °C for 12 hours, they were taken out and divided into two groups, and immersed in phosphate buffered saline (PBS) for 0.5 hour and 3 hours, respectively. Then, after washing with PBS, the samples were placed in a 24-well plate, and 1 mL of 0.1 M citrate phosphate buffer (pH = 5) containing o-phenylenediamine (1 μg / mL) and hydrogen peroxide (0.03%) was added. After 15 minutes, 2M H 2 SO 4To stop the reaction. The supernatant was collected and the optical density (OD) was detected at 492 nm using a microplate reader (SpectraMax M2). The results are shown in Table 5. The experimental results indicate that after soaking in PBS for 0.5 h and 3 h, the adhesion rates of proteins on silica gel reached 80.32% and 62.56%, respectively. In contrast, after soaking in PBS for 3 h, the adhesion rate of HRP-IgG protein on pSBMA / FDA@GOx was only 6.45%, indicating that the addition of FDA does not affect the anti-protein adhesion performance. In addition, it can be seen that the PCBMA coating further reduces protein adhesion, and the adhesion rate of non-specific proteins on the hydrogel coating of pCB / pSBMA / FDA@GOx after soaking in PBS for 3 h was only 2.86%.

[0066] Table 5 Relative HRP-IgG protein adsorption of each layer of hydrogel coating at different times

[0067]

[0068] Example 15

[0069] Anti-platelet adhesion test: Platelet-rich plasma (PRP) was obtained by centrifuging fresh rat whole blood for 15 minutes (1500 rpm). A bare silica gel catheter and a hydrogel-coated silica gel catheter (Example 12) were soaked in PBS at 37 °C for 1 h and placed in a 24-well plate with a PRP concentration of 100 μL. After incubation at 37 °C for 2 h, the surface of the sample was gently washed with PBS. The cells were fixed with 2.5% glutaraldehyde solution at 4 °C for 2 h, dehydrated successively with ethanol at different concentrations (50%, 60%, 70%, 80%, 90%, 100%) for 15 minutes, then taken out and dried at room temperature. After gold spraying, scanning electron microscopy was performed. As Figure 2 shown, where A represents the silica gel catheter and B represents the pCB / pSBMA / FDA@GOx hydrogel silica gel catheter prepared in Example 12. After 1 h of blood circulation, the bare silica gel catheter was severely blocked and there was a large amount of adhered thrombus on the inner wall. In contrast, the hydrogel-coated catheter remained unobstructed and no observable thrombus formation occurred. It shows that the hydrogel-coated catheter is beneficial for resisting platelet adhesion.

[0070] Example 16

[0071] Mouse evaluation of anti-infection effect in vivo: Six female Balb / c mice (8 weeks old, 19 - 24 g) were randomly divided into a normal group and an infection group. Each group consisted of a bare silicone catheter group (n = 3) and a pCB / pSBMA / FDA@GOx hydrogel-coated catheter group prepared in Example 12 (n = 3). The bare silicone catheter and the pCB / pSBMA / FDA@GOx hydrogel-coated catheter were pre-incubated in a Staphylococcus aureus suspension for 3 hours (OD = 0.05) before implantation. Then the catheters were implanted subcutaneously under the back skin of the mice. On the 5th day, after the mice were euthanized, the tissues around the catheters were quickly removed from the mice and placed in 4% paraformaldehyde solution for sectioning and H&E staining observation, as Figure 4 shown, Figure 4 in which A shows the effect after the application of the bare silicone catheter, and B shows the effect after the application of the pCB / pSBMA / FDA@GOx hydrogel catheter. As can be seen from Figure 4 , obvious ulcers were shown in the skin tissues at the implantation sites of the bare catheters, and no obvious changes were observed in the tissues around the hydrogel-coated catheters, indicating that the hydrogel-coated catheter has excellent biocompatibility and antibacterial effect. Digital photos of the live bacteria recovered from the infected bare catheters and the bacteria-infected hydrogel-coated catheters prepared in Example 12 are shown in Figure 5 shown, Figure 5 in which A is the bare silicone catheter and B is the pCB / pSBMA / FDA@GOx hydrogel catheter. As can be seen from Figure 5 , compared with the bare catheter, there were almost no live bacteria on the hydrogel-coated catheter, indicating that the hydrogel coating can also reduce the proliferation of bacteria.

[0072] The above-mentioned large number of test results show that the preparation method of the present invention is simple, efficient and environmentally friendly, and is friendly to the environment; the hydrogel coating is made of sulfobetaine-type and carboxybetaine zwitterions, dopamine, pluronic diacrylate, and glucose oxidase; the hydrogel coating on the medical catheter consists of a three-layer structure; the adhesive side of the hydrogel coating forms a firm adhesion through the excellent adhesion of the mussel-inspired adhesive - dopamine, and then in-situ grows a sulfobetaine-type zwitterionic hydrogel coating; finally, a carboxybetaine hydrogel coating is prepared by interpenetrating networks; the present invention has appropriate mechanical properties, anti-nonspecific protein adhesion ability, anti-cell adhesion ability, biocompatibility and excellent antibacterial effect. It has broad application prospects in the field of biomedical materials, especially as antibacterial and antithrombotic medical catheters, etc. The addition of FDA improves the anti-swelling property and mechanical properties of the hydrogel coating. GOx is encapsulated in the FDA micelles and can utilize the H 2 O 2Sterilization. Since GOx is encapsulated in micelles, the release of GOx is restricted, thus achieving a slow-release effect. Compared with the existing method of directly encapsulating GOx in hydrogels, it has the ability of long-term sterilization and anti-thrombosis.

Claims

1. A method for preparing an antibacterial and antithrombotic medical catheter, characterized in that: The steps include: 1) acrylylating the poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymer to prepare Pluronic diacrylate FDA; 2) Mixing FDA and glucose oxidase to form FDA self-assembled micelles, in which glucose oxidase is encapsulated; 3) the silicone catheter is immersed in the adhesive, and an adhesive layer is deposited on the surface of the silicone catheter; 4) mixing a sulfobetaine type zwitterionic monomer, a crosslinking agent, FDA self-assembled micelles encapsulating glucose oxidase, an oxidant, an initiator and water to prepare a prepolymer solution; 5) immersing the silicone catheter with an adhesive layer prepared in step 2) into the prepolymer solution, bonding an antibacterial and antithrombotic hydrogel coating on the surface of the silicone catheter, and then rinsing and drying; 6) soaking the silicone catheter treated in step 4) in an initiator solution; 7) Immerse the silicone catheter treated in step 5) in a carboxylic acid betaine zwitterion monomer solution, remove oxygen, and irradiate with ultraviolet light to cover the carboxylic acid betaine zwitterion on the hydrogel coating, then take it out and dry it to obtain a zwitterion-based medical catheter that can achieve antibacterial and anti-thrombotic effects.

2. The method for preparing a medical catheter for achieving antibacterial and antithrombotic properties according to claim 1, characterized in that: In step 2), the acrylic degree of the FDA self-assembled micelles is 10-15%.

3. The method for preparing a medical catheter for achieving antibacterial and antithrombotic properties according to claim 1, characterized in that: The binder in step 3) is a dopamine hydrochloride solution, and the concentration of dopamine hydrochloride is 1.0-5.0 mg / mL; the dopamine hydrochloride deposition process takes 24 hours in total, and the dopamine hydrochloride solution is replaced every 3 hours.

4. The method for preparing a medical catheter for achieving antibacterial and antithrombotic effects according to claim 1, characterized in that: The initiator is alpha-ketoglutaric acid; the oxidant is ferric chloride; the crosslinking agent is methylenebisacrylamide; the sulfobetaine type zwitterion monomer is sulfobetaine methyl methacrylate, and the carboxylic acid betaine zwitterion monomer is carboxylic acid betaine methyl methacrylate.

5. The method for preparing a medical catheter for achieving antibacterial and antithrombotic effects according to claim 1, characterized in that: In the prepolymer solution, the concentration of the sulfobetaine zwitterionic monomer is 3.0-6.0 mol / L; the concentration of the pluronic diacrylate self-assembled micelle is 50-400 mg / mL; the concentration of the crosslinking agent is 1-5 mg / mL; and the concentration of ferric chloride is 1-5 mg / mL.

6. The method for preparing a medical catheter for achieving antibacterial and antithrombotic effects according to claim 1, characterized in that: In step 5), the silicone catheter is immersed in the prepolymer solution for 30 minutes.

7. The method for preparing an antibacterial and antithrombotic medical catheter according to claim 1, characterized in that: In step 6), the immersion time of the initiator solution is 2-10 minutes.

8. The method for preparing a medical catheter for achieving antibacterial and antithrombotic effects according to claim 1, characterized in that: In step 7), deoxygenation is carried out by introducing nitrogen or an inert gas to reduce the solubility of oxygen; the concentration of the carboxylic acid betaine zwitterion is 3.0-6.0 mol / L; the wavelength of the ultraviolet light is 350-380 nm, and the irradiation time is 6-12 h.

9. A medical catheter with antibacterial and antithrombotic properties prepared by the preparation method according to any one of claims 1 to 8.

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